Luini A, Goldberg O, Teichberg V I
Proc Natl Acad Sci U S A. 1981 May;78(5):3250-4. doi: 10.1073/pnas.78.5.3250.
Specific 22Na+ efflux rates from preloaded rat striatal slices are increased in a dose-dependent manner by L-glutamate and other excitatory amino acids displaying the following order of efficiency: N-methyl-D-aspartate greater than DL-homocysteate greater than quisqualate greater than kainate greater than D-glutamate greater than L-glutamate greater than L-aspartate. Amino acid antagonists such as 2-amino-5-phosphonovalerate, gamma-D-glutamylglycine, DL-aminosuberate, DL-aminoadipate, and diethyl glutamate but not nonexcitatory amino acids such as gamma-aminobutyric acid inhibit the amino acid-induced increase in specific 22Na+ efflux rate. Increased K+ concentrations, in the presence of 2 mM Ca2+, increase the specific 22Na+ efflux. The latter and the response to N-methyl-D-aspartate, but not the responses to L-glutamate, L-aspartate, quisqualate, and kainate, are inhibited to similar extents by the same antagonists. These results suggest the release from striatal nerve terminals of a putative neurotransmitter with pharmacological properties different from those of L-glutamate or L-aspartate but similar to those of N-methyl-D-aspartate. The results of this study show that the stimulation of the 22Na+ efflux in brain slices by neuroactive amino acids and K+ ions is a valid and powerful tool for pharmacological investigations of excitatory amino acid receptors and their putative ligands.
预先加载的大鼠纹状体切片中特定的22Na+流出率,会以剂量依赖的方式被L-谷氨酸和其他兴奋性氨基酸提高,这些氨基酸呈现出以下效率顺序:N-甲基-D-天冬氨酸>DL-高半胱氨酸>喹啉酸>海人酸>D-谷氨酸>L-谷氨酸>L-天冬氨酸。氨基酸拮抗剂如2-氨基-5-磷酸戊酸、γ-D-谷氨酰甘氨酸、DL-氨基辛酸盐、DL-氨基己酸盐和谷氨酸二乙酯,但非兴奋性氨基酸如γ-氨基丁酸,会抑制氨基酸诱导的特定22Na+流出率增加。在存在2 mM Ca2+的情况下,增加K+浓度会提高特定的22Na+流出率。后者以及对N-甲基-D-天冬氨酸的反应,但对L-谷氨酸、L-天冬氨酸、喹啉酸和海人酸的反应不会,会被相同的拮抗剂以相似程度抑制。这些结果表明,从纹状体神经末梢释放出一种假定的神经递质,其药理特性不同于L-谷氨酸或L-天冬氨酸,但与N-甲基-D-天冬氨酸相似。本研究结果表明,神经活性氨基酸和K+离子对脑切片中22Na+流出的刺激,是用于兴奋性氨基酸受体及其假定配体药理学研究的一种有效且强大的工具。